The objective is to characterize the biochemical and genetical mechanisms of obligate intracellular parasitism between the eukaryotic host and prokaryotic parasite. Molecular interactions at the cell surface and with soluble components are being investigated as primary determinants of metabolic cooperation between host and parasite. An insight into the biochemical strategy of obligate intracellular parasitism of phagocytic cells has been achieved by studying the in vitro metabolic capabilities and in vivo effect of lysosomotropic amines on the growth of Coxiella burnetii. A pathogenic mechanism based on regulation of microbial metabolism by H-dependent stimulation of cell function has been described for C. burnetii, the etiologic agent of Q fever. This organism is a gram-variable and sporogenic obligate intracellular parasite which multiplies only in the phagolysosome of eukaryotic cells. Thus, a key feature of phagolysosomal growth of C. burnetii is a membrane structurally and functionally compatible with an otherwise hostile environment. Our recent studies support the hypothesis that intracellular parasites have evolved metabolic programs complementary to the cellular compartment in which they reside.